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目的研究新的血管生成抑制剂2(8羟基6甲氧基1氧1氢2苯并吡喃3烃基)丙酸(NM3)对胃癌生长的抑制作用,并探讨其对胃癌细胞凋亡的影响。方法建立人胃腺癌裸鼠皮下异体移植模型。移植1周后开始腹腔注射NM3,隔天1次,剂量为10、20、40mg/kg,分别3d1次联合卡铂5mg/kg,并与生理盐水对照组、NM3或卡铂单独治疗组比较(NM3用5周,卡铂4周)。种植后第7周处死动物,测量肿瘤大小,计算抑瘤率,流式细胞术(FCM)法分析肿瘤细胞凋亡指数(AI)。结果单用NM3剂量分别为10、20及40mg/kg时,肿瘤的平均重量分别为(1351.0±116.9)、(1041.1±143.5)及(767.5±140.1)mg,明显小于生理盐水对照组[(1754.0±144.2)mg,P<0.05]。单用卡铂组的抑瘤率为5.6%,对胃癌无明显抑制作用。单用NM3剂量为10、20及40mg/kg时,抑瘤率分别为23.0%、40.6%及56.2%。三组剂量分别联合卡铂治疗时抑瘤率为42.9%、47.6%及63.2%,与对照组比较差异有统计学意义(P<0.05)。NM3三种剂量组联合卡铂治疗的AI分别是(6.96±0.65)%、(10.65±1.43)%及(21.66±2.96)%,对照组为(1.37±0.19)%,卡铂组为(1.85±0.22)%。结论NM3能诱导胃癌细胞凋亡,对体内胃癌的生长有抑制作用,能加强卡铂对胃癌的化疗疗效。
Objective To study the inhibitory effect of NMDA 2, a novel angiogenesis inhibitor 2, on the growth of gastric cancer and its effect on the apoptosis of gastric cancer cells . Methods Human gastric adenocarcinoma subcutaneous allograft model was established. One week after the transplantation, intraperitoneal injection of NM3 was given and the dosage was 10, 20 and 40 mg / kg, respectively, 3 days and 5 mg / kg carboplatin respectively. Compared with the saline control group, NM3 or carboplatin alone group NM3 for 5 weeks, carboplatin for 4 weeks). The animals were sacrificed on the 7th week after implantation. The tumor size was measured. The tumor inhibition rate was calculated. The apoptosis index (AI) was analyzed by flow cytometry (FCM). Results The mean tumor weights were (1351.0 ± 116.9), (1041.1 ± 143.5) and (767.5 ± 140.1) mg at 10, 20 and 40 mg / kg, respectively, which were significantly lower than those in the saline control group ± 144.2) mg, P <0.05]. Carboplatin alone had a tumor inhibition rate of 5.6%, which showed no significant inhibitory effect on gastric cancer. The inhibition rates of NMO alone at 10, 20 and 40 mg / kg were 23.0%, 40.6% and 56.2%, respectively. The inhibition rates of the three groups when combined with carboplatin were 42.9%, 47.6% and 63.2%, respectively, which were significantly different from those of the control group (P <0.05). The AI of the three doses of NM3 combined with carboplatin were (6.96 ± 0.65)%, (10.65 ± 1.43)% and (21.66 ± 2.96)% in the control group and (1.37 ± 0.19)% in the control group and ± 0.22)%. Conclusion NM3 can induce the apoptosis of gastric cancer cells and inhibit the growth of gastric cancer in vivo, which can enhance the curative effect of carboplatin on gastric cancer.